Low Dose Naltrexone (LDN): The New Treatment You've Never Heard of...

Low Dose Naltrexone (LDN):  The treatment you've never heard of...

Why haven't you heard about this amazing new breakthrough for conditions ranging from autoimmunity to cancer?  Perhaps because as of yet no company has stepped forward with the billions of dollars needed to do a large-scale study on low-dose naltrexone (LDN).  Unfortunately getting FDA-approval for use is not a straightforward process.  With the patent expired, no drug company has been willing to pay such a large sum when they cannot sell the drug exclusively.

However, if you check PubMed, there are currently over 90 studies published on the various uses of LDN, from pain relief, fibromyalgia, Crohn's disease, multiple sclerosis, systemic sclerosis and even cancer.  I have been using this drug in clinical practice with great results for the past several years and I want to tell you about it...

So how does LDN work?

Researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania have discovered the mechanism by which a low dose of the opioid antagonist naltrexone, an agent used clinically (off-label) to treat cancer and autoimmune diseases, exerts a profound inhibitory effect on cell proliferation. We believe that opioid receptor blockade by LDN provokes a compensatory elevation in endogenous opioids and opioid receptors that can function even after LDN is no longer available.

These papers revealed that a short-term opioid receptor blockade with naltrexone (LDN), a general opioid receptor antagonist devoid of intrinsic activity, results in an elevation in production of your own opioids and in response to the blockade. Interference of opioid peptide–opioid receptor interactions for a short time each day (from 4-6 hours) with LDN provided a subsequent window of time (18–20 hours) for the increased levels of endogenous opioids and opioid receptors to elicit a robust functional response: the inhibition of cell proliferation.  In addition many patient report an improved sense of well-being and decrease in overall pain, as one might expect with higher levels of opioid production in the body.

Preliminary Research Abounds for cancer and autoimmune disease

Low dose of the opioid antagonist naltrexone (LDN) is being used clinically off-label to treat cancer and autoimmune diseases, by exerting a profound inhibitory effect on cell proliferation.  LDN is an oral medication, generic, inexpensive, and non-toxic, and has been documented to alter the course of both neoplasias and autoimmune diseases such as Crohn's and multiple sclerosis, making this drug especially attractive as a therapeutic agent.

According to this study in Clinical Rheumatology, Low Dose Naltrexone(LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. They suggest that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated.

A study published online in the Cochraine Library in February 2014 discusses using low-dose naltrexone to induce remission in Crohn's Disease.  Although the author conclude there is insufficient evidence to recommend and further research is needed, data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn’s disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo.

In the Journal of Clinical Gastroenterology April 2013, Naltrexone therapy appears safe with limited toxicity when given to children with Crohn’s disease and may even reduce disease activity.

Complex Regional Pain Syndrome (CRPS) is a neuropathic pain syndrome involves glial activation and central sensitization in the central nervous system. This can be a difficult disease to treat and patients suffer greatly with severe chronic pain.   An article in the Journal of Neuroimmune Pharmacology showed positive outcomes of two CRPS patients, after they were treated with low-dose naltrexone, in combination with other CRPS therapies.  Perhaps this is because Low Dose Naltrexone (LDN) is known to antagonize the Toll-like Receptor 4 (TLR4) pathway and attenuate activated microglia.

Link to Fibromyalgia and Autism?

Another article posted online in Discovery Medicine came to the following conclusions:

1. Patients on chronic opioids relate autistically.
2. Autism is a hyperopioidergic disorder.
3. Fibromylagia is a hypoopioidergic disorder.
4. Low opioid tone caused by opioid maintenance or fibromyalgia can usually be reversed with low-dose naltrexone.
5. The increase in the incidence of autism may have been caused by the increase in use of opioids for analgesia during childbirth.

The bottom line is that for disorders that involve low endogenous opioid production, like fibromyalgia and chronic fatigue syndrome, Low Dose Naltrexone may prove to be profoundly beneficial.

A January 2013 article written in Arthritis and Rheumatology concluded that evidence continues to show that low dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated.

Motility Agent for Small Intestinal Bacterial Overgrowth (SIBO)

Another novel use of Low Dose Naltrexone has been for aiding motility in SIBO (small intestinal bacterial overgrowth).  Ploesser et al described the use of LDN for aiding the migrating motor complex (MMC) in cleansing the small bowel.  His small study use 2.5mg twice daily in patients with IBS and evidence of SIBO and 4.5mg daily in patients with inflammatory bowel disease.  Approximately 68% of the study patients had improvement in symptoms taking LDN.  According to other research, LDN may have effects on the gut to decrease inflammation, decrease intestinal permeability and stabilize toll like receptors, in addition to aiding motility.

Experimental and Off-label but well tolerated and promising

The use of LDN for chronic disorders is still experimental and considered off-label.  This doesn't stop progressive doctors from prescribing it due to it's safety profile.  The typical dose of LDN is a compounded immediate release tablet from 1.5 to 4.5mg taken at bedtime.   The few reported side effects may be related to opioid blockade at night.  Occasionally patients report anxiety, insomnia, vivid dreaming or nightmares.  There are a portion of patients who already have elevated opioids that may not tolerate the drug. To avoid side effects, I generally start patients on half of intended dose and increase after 7-10 days.  If they still report symptoms, we move the dosing earlier in the day and may still get a beneficial effect.

Low Dose Naltrexone is an oral medication, generic, inexpensive, and non-toxic, and has been documented to alter the course of both neoplasias and autoimmune diseases such as Crohn's and multiple sclerosis, making it an attractive and effective therapeutic agent.

For more on LDN watch my recent interview with Dr. Alex Vasquez ...

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More References:

1. Low Dose Naltrexone Research Trust
2. LDN Clinical Trials 

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How to Heal a Leaky Gut, Part II

Did you miss my first Leaky Gut Article?! Read more here

So now you may be wondering if you have leaky gut...

Food allergies, toxins, sugar, antibiotics, parasites and stress can wreak havoc with your gastrointestinal system, upsetting the balance in your intestine as well as allowing harmful substances to enter the system. Gas, bloating, diarrhea, constipation or abdominal discomfort may be the first clue that something is wrong with the digestive tract, but did you know allergies
or even lack of energy and fatigue can often be traced to digestive problems as well?

Normally the gastrointestinal epithelium provides a semi-permeable barrier with allows nutrients to be absorbed while preventing larger molecules from crossing into the bloodstream. When this lining becomes inflamed or damaged, then the barrier becomes "leaky". The fallout results in larger, undigested food molecules and other “bad stuff” (yeast, toxins, and all other forms of waste) that your body normally doesn’t allow through, to flow freely into your bloodstream.

Causes of increased intestinal hyperpermeability or "leaky gut":

• Medications (NSAIDS) like ibuprofen and motrin
• Microbial overgrowth or infection
• Parasite infections
• Fungal overgrowth (Candida)
• Ingestion of allergenic foods
• Maldigestion/malabsorption (pancreatic insufficieny or low HCl)
• Radiation therapy or chemotherapy
• Stress
• Aging
• IgA deficiency
• Chronic alcohol intake
• Excessive or strenuous exercise
• Inflammatory bowel disease - Crohn's or Ulcerative colitis

The small and large intestines contains numerous dietary and bacterial products with toxic properties. These include bacteria, bacterial cell wall (LPS), peptides, and bacterial antigens capable of inducing antibodies which may cross-react with human tissues.... when these antibodies react, they may form systemic immune complexes which can circulate and deposit in tissues far away from the gut.

Abnormalities of the gut lining barrier lead to increased uptake of inflammatory molecules and pathogenic bacteria. With inflammation & injury to the gut lininng, mucosal absorption of normally-excluded substances increases dramatically. Intestinal inflammation enhances the uptake and distribution of potentially injurious bacteria and proteins .

Leaky Gut is seen in disorders such as:

• Inflammatory bowel disease (Crohn's & Colitis)
• Inflammatory joint disease
• Food allergy
• Celiac disease
• Rheumatoid arthritis
• Ankylosing spondylitis
• Reiter’s syndrome
• Eczema & psoriasis
• Bipolar, depression and schizophrenia
• Allergies and asthma
• Autoimmune thyroiditis
• Multiple sclerosis
• Autoimmune liver & gallbladder disease

So how do we test for "Leaky Gut"?

Small molecules (glucose or mannitol) readily penetrate cells and passively diffuse through them. Larger molecules such as lactulose are normally are normally not able to diffuse through the cell. If the tight junctions between the cells are functioning properly, they will prevent the lactulose from leaking through. The Intestinal Permeability Test directly measures the ability these two sugar molecules—mannitol and lactulose—to permeate the intestinal mucosa.

Mannitol is readily absorbed and serves as a marker of transcellular uptake. Lactulose is only slightly absorbed and serves as a marker for mucosal integrity (ability of those "tight junctions" to keep out the bad stuff) The test is a 6 hour urine test that compares ratios of the two substances.

For more info:

Genova Diagnostics Intestinal Permeability Assessment
You will need to contact your functional medicine physician in order to order the test.
Now for some treatment options for this leaky gut!

Nutritional Support

1. Glutamine, an amino acid, has been shown to reverse intestinal mucosal damage from various insults. Glutamine is the principle fuel used by the upper intestinal tract to repair and heal.
2. Agents that stimulate protective mucus secretion may also help with the healing. Some common ones I use are marshmallow root extract and deglycyrrhizinated licorice (DGL) extract.
3. Probiotics are essential! Lactobacillus casei, bifidobacter species, and saccromyces boulardii, a beneficial type of yeast are all important to restore gut health.
4. Fish oil can be very helpful in the treatment of intestinal inflammation by decreasing inflammatory prostaglandins. EPA and DHA should be used in the range of 2-4gm daily
5. Quercetin functions as a natural mast cell stabilizer and decrease release of histmine which contributes to inflammation & injury. To be effective, quercetin should be used in powder form and taken 3-6gm daily.
6. Vitamins A and D are critical to supporting secretory IgA function and restoring the mucosal immune system. Ask your doctor for specific doses...

To Decrease Toxic Load:

• Eliminate all known foods that you are sensitive to. This can be determined through a comprehensive elimination diet or IgG/IgE food tests on the blood.
• Avoid alcohol, NSAIDS (ibuprofen, motrin, alleve), and minimize other medications.
• Bentonite clay is a well-known intestinal adsorbent which absorbs numerous toxins, endotoxins and bacteria. Its value in permeability alterations may result from lowering the toxin load in the lumen, thus facilitating repair. I also frequently recommend Upgraded charcoal tabs for the same purpose.
• HCI and digestive enzymes such as plant enzymes, pepsin and pancreatin might help to lessen the antigenic load or toxic molecules being presented on the intestinal lining.

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Dr. Jill's Story

When you meet Dr. Jill, you will immediately sense her compassion and genuine desire to help people find answers and give them hope that they can feel healthy again.  What you may not know is that her own journey through life-threatening illness was a powerful force in shaping her passion for teaching people how to heal through functional medicine.  Read her story here… 

My Story

Since my childhood, I have always been passionate about seeking answers to complex problems. I believed that the human body could regain health given the right tools.  However, it wasn’t until June of 2001 that I had very personal encounter with my own mortality.  It was then I had put this belief into action...

Sudden Turn of Events … from Doctor to Patient

During my 3^rd year of training in medicine at Loyola University in Chicago, I found an unusual lump in my left breast and with my husband’s insistence; I proceeded to schedule an ultrasound and biopsy.  Although I scheduled the tests, I was not too concerned that this lump might signify something more serious.  A few days later however, my worst nightmare was confirmed with a call from the surgeon.  She said yes, despite all of the statistics against it at the age of twenty-five years old, I had invasive ductal carcinoma (i.e. breast cancer).  I was devastated!  This sudden news sent my very orderly world spinning as I began to process what the next 12 months would hold… several more surgeries, six rounds of aggressive chemotherapy followed by many weeks of radiation, ugh!  I literally went from doctor to patient overnight.  The rest of that year was a blur as I took a leave of absence from medical school to complete this harsh treatment regimen.  During this time, an important part of my plan included nutritional supplementation, daily exercise and prayers for healing.   By the summer of 2002, I had officially “beaten” the cancer but nearly destroyed my body in the process.  Completely bald, malnourished, and down to my lowest weight since fourteen, I was physically depleted but mentally and emotionally still in the game.

From Surviving to Thriving…

At this point, although I had just beaten cancer, I was determined to go further.  My desire was to go from surviving to a place of thriving… full of energy and life!  My unwavering faith in God and my passion for nutrition became instrumental in turning my health around.  The battle against an aggressive deadly breast cancer was only the beginning of my journey.  Six months after completing therapy and returning to medical school, I was once again diagnosed with a very serious medical condition.

Round Two: a Second Diagnosis…

The following year I was diagnosed with Crohn’s disease, a very painful autoimmune disease, in which the body’s own immune system attacks the gastrointestinal lining, causing nutrient depletion, cyclical fevers, fatigue, weakness and ongoing abdominal pain.  Undoubtedly connected to the toxic effect of   chemotherapy on my gut lining, I was determined to beat this new threat as well. In the beginning, my gastroenterologist told me point blank, “Diet has nothing to do with this.”  He also gave me the prognosis that I would need multiple surgeries over my lifetime and would never be completely cured. I was given powerful medications to calm the inflammation, but they did nothing for my symptoms.  I was told that I would require steroids and immune-suppressing medications to control the disease.   Refusing to believe that surgery and medications were the only options, I studied extensively on the healing power of nutritious food and dietary changes.   I began by making major changes in my own diet, eliminating gluten, dairy, and all processed foods and eating nutrient dense options instead.  I also consulted with a wise naturopath who taught me the power of appropriate nutritional supplementation in restoring health and energy and healing the inflammation in my gut.

Back to Optimal Health!

“This sickness will not lead to death... It is for the glory of God” John 11:4

Now over twelve years later, after relentless pursuit of personal healing I am currently in the best health of my life, completely free of breast cancer and healed from Crohn’s disease!   I continue to eat an organic, whole food, gluten-free Paleo-style diet, exercise regularly, and practice my faith through prayer and meditation. It is evident that God healed my body expressly for the purpose of helping others and thus, I am committed to helping people find answers and live vibrantly through functional medicine. More than ever before, I believe that the human body can regain health if given the right tools… and I am living proof!

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